FDA Label for Asacol

Description

Each Asacol delayed-release tablet for oral administration contains 400 mg of mesalamine, an anti-inflammatory drug. The Asacol delayed-release tablets are coated with acrylic based resin, Eudragit S (methacrylic acid copolymer B, NF), which dissolves at pH 7 or greater, releasing mesalamine in the terminal ileum and beyond for topical anti-inflammatory action in the colon. Mesalamine has the chemical name 5-amino-2-hydroxybenzoic acid; its structural formula is:

Chemical Structure - asacol 01

Clinical Pharmacology

Mesalamine is thought to be the major therapeutically active part of the sulfasalazine molecule in the treatment of ulcerative colitis. Sulfasalazine is converted to equimolar amounts of sulfapyridine and mesalamine by bacterial action in the colon. The usual oral dose of sulfasalazine for active ulcerative colitis is 3 to 4 grams daily in divided doses, which provides 1.2 to 1.6 grams of mesalamine to the colon.

The mechanism of action of mesalamine (and sulfasalazine) is unknown, but appears to be topical rather than systemic. Mucosal production of arachidonic acid (AA) metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs), is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin (PG) production in the colon.

Indications And Usage

Asacol tablets are indicated for the treatment of mildly to moderately active ulcerative colitis and for the maintenance of remission of ulcerative colitis.

Contraindications

Asacol tablets are contraindicated in patients with hypersensitivity to salicylates or to any of the components of the Asacol tablet.

Adverse Reactions

Asacol tablets have been evaluated in 3685 inflammatory bowel disease patients (most patients with ulcerative colitis) in controlled and open-label studies. Adverse events seen in clinical trials with Asacol tablets have generally been mild and reversible. Adverse events presented in the following sections may occur regardless of length of therapy and similar events have been reported in short- and long-term studies and in the post-marketing setting.

In two short-term (6 weeks) placebo-controlled clinical studies involving 245 patients, 155 of whom were randomized to Asacol tablets, five (3.2%) of the Asacol patients discontinued Asacol therapy because of adverse events as compared to two (2.2%) of the placebo patients. Adverse reactions leading to withdrawal from Asacol tablets included (each in one patient): diarrhea and colitis flare; dizziness, nausea, joint pain, and headache; rash, lethargy and constipation; dry mouth, malaise, lower back discomfort, mild disorientation, mild indigestion and cramping; headache, nausea, aching, vomiting, muscle cramps, a stuffy head, plugged ears, and fever.

Adverse events occurring in Asacol-treated patients at a frequency of 2% or greater in the two short-term, double-blind, placebo-controlled trials mentioned above are listed in Table 1 below. Overall, the incidence of adverse events seen with Asacol tablets was similar to placebo.

Of these adverse events, only rash showed a consistently higher frequency with increasing Asacol dose in these studies.

In a 6-month placebo-controlled maintenance trial involving 264 patients, 177 of whom were randomized to Asacol tablets, six (3.4%) of the Asacol patients discontinued Asacol therapy because of adverse events, as compared to four (4.6%) of the placebo patients. Adverse reactions leading to withdrawal from Asacol tablets included (each in one patient): anxiety; headache; pruritus; decreased libido; rheumatoid arthritis; and stomatitis and asthenia.

In the 6-month placebo-controlled maintenance trial, the incidence of adverse events seen with Asacol tablets was similar to that seen with placebo. In addition to events listed in Table 1, the following adverse events occurred in Asacol-treated patients at a frequency of 2% or greater in this study: abdominal enlargement, anxiety, bronchitis, ear disorder, ear pain, gastroenteritis, gastrointestinal hemorrhage, infection, joint disorder, migraine, nervousness, paresthesia, rectal disorder, rectal hemorrhage, sinusitis, stool abnormalities, tenesmus, urinary frequency, vasodilation, and vision abnormalities.

In 3342 patients in uncontrolled clinical studies, the following adverse events occurred at a frequency of 5% or greater and appeared to increase in frequency with increasing dose: asthenia, fever, flu syndrome, pain, abdominal pain, back pain, flatulence, gastrointestinal bleeding, arthralgia, and rhinitis.

In addition to the adverse events listed above, the following events have been reported in clinical studies, literature reports, and postmarketing use of products which contain (or have been metabolized to) mesalamine. Because many of these events were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to their seriousness or potential causal connection to mesalamine:

Body as a Whole: Neck pain, facial edema, edema, lupus-like syndrome, drug fever (rare).

Cardiovascular: Pericarditis (rare), myocarditis (rare).

Gastrointestinal: Anorexia, pancreatitis, gastritis, increased appetite, cholecystitis, dry mouth, oral ulcers, perforated peptic ulcer (rare), bloody diarrhea. There have been rare reports of hepatotoxicity including, jaundice, cholestatic jaundice, hepatitis, and possible hepatocellular damage including liver necrosis and liver failure. Some of these cases were fatal. Asymptomatic elevations of liver enzymes which usually resolve during continued use or with discontinuation of the drug have also been reported. One case of Kawasaki-like syndrome which included changes in liver enzymes was also reported.

Hematologic: Agranulocytosis (rare), aplastic anemia (rare), thrombocytopenia, eosinophilia, leukopenia, anemia, lymphadenopathy.

Musculoskeletal: Gout.

Nervous: Depression, somnolence, emotional lability, hyperesthesia, vertigo, confusion, tremor, peripheral neuropathy (rare), transverse myelitis (rare), Guillain-Barré syndrome (rare).

Respiratory/Pulmonary: Eosinophilic pneumonia, interstitial pneumonitis, asthma exacerbation, pleuritis.

Skin: Alopecia, psoriasis (rare), pyoderma gangrenosum (rare), dry skin, erythema nodosum, urticaria.

Special Senses: Eye pain, taste perversion, blurred vision, tinnitus.

Urogenital: Renal Failure (rare), interstitial nephritis, minimal change nephropathy (See also Renal subsection in PRECAUTIONS). Dysuria, urinary urgency, hematuria, epididymitis, menorrhagia.

Laboratory Abnormalities: Elevated AST (SGOT) or ALT (SGPT), elevated alkaline phosphatase, elevated GGT, elevated LDH, elevated bilirubin, elevated serum creatinine and BUN.

Overdosage

Two cases of pediatric overdosage have been reported. A 3-year-old male who ingested 2 grams of Asacol tablets was treated with ipecac and activated charcoal; no adverse events occurred. Another 3-year-old male, approximately 16 kg, ingested an unknown amount of a maximum of 24 grams of Asacol crushed in solution (i.e., uncoated mesalamine); he was treated with orange juice and activated charcoal, and experienced no adverse events. In dogs, single doses of 6 grams of delayed-release Asacol tablets resulted in renal papillary necrosis but were not fatal. This was approximately 12.5 times the recommended human dose (based on a dose of 2.4 g/day in a 50 kg person). Single oral doses of uncoated mesalamine in mice and rats of 5000 mg/kg and 4595 mg/kg, respectively, or of 3000 mg/kg in cynomolgus monkeys, caused significant lethality.

How Supplied

Asacol tablets are available as red-brown, capsule-shaped tablets containing 400 mg mesalamine and imprinted “Asacol NE” in black.

They are supplied by State of Florida DOH Central Pharmacy as follows:

Store at controlled room temperature 20°- 25°C (68°- 77°F) [See USP].

Principal Display Panel - 400 Mg Tablet Bottle

NDC 53808-0205-1

Asacol^®
(mesalamine)
delayed-release tablets

400 mg per tablet

Not Bioequivalent
to Asacol HD

Rx Only

30 Tablets
asacol.com